Abstract
Both slow-twitch and fast-twitch muscles are undifferentiated after birth as to their contractile protein phenotype. Thus we examined the separate and combined effects of spaceflight (SF) and thyroid deficiency (TD) on myosin heavy chain (MHC) gene expression (protein and mRNA) in muscles of neonatal rats (7 and 14 days of age at launch) exposed to SF for 16 days. Spaceflight markedly reduced expression of the slow, type I MHC gene by approximately 55%, whereas it augmented expression of the fast IIx and IIb MHCs in antigravity skeletal muscles. In fast muscles, SF caused subtle increases in the fast IIb MHC relative to the other adult MHCs. In contrast, TD prevented the normal expression of the fast MHC phenotype, particularly the IIb MHC, whereas TD maintained expression of the embryonic/neonatal MHC isoforms; this response occurred independently of gravity. Collectively, these results suggest that normal expression of the type I MHC gene requires signals associated with weight-bearing activity, whereas normal expression of the IIb MHC requires an intact thyroid state acting independently of the weight-bearing activities typically encountered during neonatal development of laboratory rodents. Finally, MHC expression in developing muscles is chiefly regulated by pretranslational processes based on the tight relationship between the MHC protein and mRNA data.
Highlights
At least four adult myosin heavy chain (MHC) genes have been identified in limb muscles, and these genes have been designated as the slow, fast IIa, fast IIx, and fast IIb MHCs in increasing order of their putative ATPase activity and fiber-shortening properties [3, 5, 34]
In studies on developing rodent neonatal skeletal muscle, it is apparent that both antigravity and locomotor muscles are in an undifferentiated state with regard to MHC gene expression following birth [2, 11, 30, 41]; during the first 3–4 wk of development, these muscles undergo both rapid growth and a marked transformation in the expression of their respective adult MHC phenotypes [2]
The experiments reported provided a rare opportunity to study MHC gene expression, in the context of both spaceflight and thyroid state, from a different perspective in which the target muscles were manipulated by these imposed variables at a time when the limb muscles were still phenotypically in an undifferentiated state (Tables 2–5)
Summary
In studies on developing rodent neonatal skeletal muscle, it is apparent that both antigravity (e.g., soleus) and locomotor (plantaris) muscles are in an undifferentiated state with regard to MHC gene expression following birth [2, 11, 30, 41]; during the first 3–4 wk of development, these muscles undergo both rapid growth and a marked transformation in the expression of their respective adult MHC phenotypes [2]. In the absence of T3 availability, expression of the slow (type I) MHC gene is augmented in both antigravity and locomotor muscles of developing animals, while, at the same time, the embryonic and neonatal isoforms are retained, thereby maintaining the muscles used for locomotion in a partially undifferentiated state [2, 6, 17]
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